Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA)

• Decrease the composite endpoint of total mortality, disabling stroke, serious bleeding, and cardiac arrest. [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Total mortality, disabling stroke, serious bleeding, or cardiac arrest [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Total mortality or cardiovascular hospitalization [ Time Frame: From date of enrollment until date of death or CV hospitalization ] [ Designated as safety issue: Yes ]
• Cardiovascular death [ Time Frame: From date of enrollment until date of death ] [ Designated as safety issue: Yes ]
• Cardiovascular death or disabling stroke [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Arrhythmic death or cardiac arrest [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Heart failure death [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Freedom from recurrent AF [ Time Frame: From date of therapy initiation until date of first AF recurrence following a 90 day wait period ] [ Designated as safety issue: No ]
• Cardiovascular hospitalization [ Time Frame: From date of enrollment until date of hospitalization ] [ Designated as safety issue: Yes ]
• Medical costs, resource utilization, and cost effectiveness [ Time Frame: From date of enrollment through follow-up (up to 5 years) ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: At months 3, 6, 12, 18, 24, 30, 36 ] [ Designated as safety issue: No ]
• Composite adverse events [ Time Frame: From date of enrollment until date of event ] [ Designated as safety issue: Yes ]
• Left atrial size, morphology and function [ Time Frame: Baseline and 3 months post therapy initiation ] [ Designated as safety issue: No ]

• Composite endpoints of total mortality, disabling stroke, serious bleeding, and cardiac arrest in patients with untreated or incompletely treated AF warranting therapy. [ Time Frame: 6 month intervals, duation of trial ] [ Designated as safety issue: Yes ]
• Cardiovascular hospitalization [ Time Frame: 6 month intervals, length of trial ] [ Designated as safety issue: Yes ]
• Freedom from recurrent AF [ Time Frame: Monitored monthly for trial duration ] [ Designated as safety issue: Yes ]
• Medical costs, resource utilization, and cost effectiveness [ Time Frame: 6 month intervals, length of trial ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: at months 3,6,12,18,24,30,36 ] [ Designated as safety issue: No ]
• Composite adverse events [ Time Frame: 6 month intervals, duration of trial ] [ Designated as safety issue: Yes ]
• LA size, morphology and function [ Time Frame: Baseline and 3 month post therapy initiation ] [ Designated as safety issue: No ]

The (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) CABANA Trial has the overall goal of establishing the appropriate roles for medical and ablative intervention for atrial fibrillation (AF). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for reducing total mortality in patients with untreated or incompletely treated AF.

The need for this trial arises out of 1) the rapidly increasing number of pts > 60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radio-frequency catheter ablation without appropriate evidence-based validation, and 4) the expanding impact of AF on health care costs.

This study will randomize 3000 patients to a strategy of catheter ablation versus pharmacologic therapy with rate or rhythm control drugs. Each pt will have 1) characteristics similar to AFFIRM pts (≥65 yo or <65 with >1 risk factor for stroke, 2) Documented AF warranting treatment, and 3) Eligibility for both catheter ablation and ≥2 anti-arrhythmic or ≥3 rate control drugs. Pts will be followed every 6 months for >2 yrs and will undergo repeat trans-telephonic monitor, Holter monitor, and CT/MR studies to assess the impact of treatment.

The CABANA trial will disclose the role of medical and non-pharmacologic therapies for AF, establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.

• Atrial Fibrillation
• Arrhythmia

• Device: Left atrial ablation

  St. Jude: Livewire, Therapy Dual/Thermocouple

  Biosense Webster: NAVI-STAR Thermo-cool,NAVI-STAR/NAVI-STAR DS, Celsius Braided Tip

  CryoCath Technologies: Freezor/Freezor MAX, Artic Front Cardiac Cryoablation catheter

  Bard: Stinger

  Boston Scientific: Blazer II RF/RPM/SteeroCath/XP, Chilli Cooled.

• Drug: Rate or Rhythm Control Therapy

  Rate control: Metoprolol 50-100mg, Atenolol 50-100mg, Propranolol 40-80mg, Acebutolol 200-300mg, Carvedilol 6.25-25mg, Diltiazem 180-240mg, Verapamil 180-240mg, Digoxin 0.125-0.25mg

  Rhythm control: Propafenone 450-625mg, Flecainide 200-300mg, Sotalol 240-320mg, Dofetilide 500-1000mcg, Amiodarone 200-400mg, Quinidine 600-900mg

• Active Comparator: Left Atrial Ablation
  Pulmonary vein isolation using a circumferential ablative approach in the left atrium. Ablation may be performed using circular mapping catheter-guided ablation, antral isolation using a circular guided approach, or wide area circumferential ablation.
  Intervention: Device: Left atrial ablation
• Active Comparator: Rate or Rhythm Control Therapy
  Current state-of-the-art drug therapy for atrial fibrillation (rate control or rhythm control). Treating physicians will be encouraged to follow the American College of Cardiology / American Heart Association / European Society of Cardiology Atrial Fibrillation Guidelines with regard to drug therapy for atrial fibrillation. The specific choice of rate control versus rhythm control drug therapy and the specific drugs to be used will ultimately be left to the discretion of the treating physician.
  Intervention: Drug: Rate or Rhythm Control Therapy

Inclusion Criteria:

• Have the capacity to understand and sign an informed consent form
• Be ≥18 years of age.
• Have documented AF episodes ≥1 hour in duration; with ≥2 episodes over 4 months with electrocardiographic documentation of 1 episode or at least 1 episode of AF lasting more than 1 week
• Warrant active therapy beyond simple ongoing observation
• Be eligible for both catheter ablation and ≥2 sequential rhythm control and/or ≥3 rate control drugs.
• Be ≥65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension, Diabetes, Congestive heart failure, Prior stroke or TIA, LA size ≥5.0 cm (or volume index ≥40 cc/m2), or EF ≥35. Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or LV hypertrophy to qualify.

Exclusion Criteria:

• Lone AF in the absence of risk factors for stroke in patients <65 years of age
• Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
• Patients who have failed ≥2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy
• More than one week of amiodarone treatment in the past 3 months
• An efficacy failure of full dose amiodarone treatment ≥12 weeks duration at any time
• Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
• Recent cardiac events including MI, PCI, or valve or bypass surgery in the preceding 3 months
• Hypertrophic obstructive cardiomyopathy
• Class IV angina or Class IV CHF (including past or planned heart transplantation)
• Other mandated anti-arrhythmic drug therapy
• Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
• Prior LA catheter ablation with the intention of treating AF
• Prior surgical interventions for AF such as the MAZE procedure
• Prior AV nodal ablation
• Patients with other arrhythmias requiring ablative therapy
• Contraindication to warfarin anti-coagulation
• Renal failure requiring dialysis
• Medical conditions limiting expected survival to <1 year
• Women of childbearing potential (unless post-menopausal or surgically sterile)
• Participation in any other clinical mortality trial
• Unable to give informed consent

• National Heart, Lung, and Blood Institute (NHLBI)
• St. Jude Medical
• Biosense Webster, Inc.